Sulforaphane and Organosulfurs in Cruciferous Vegetables

The Living Force

I posted about this elsewhere but I thought it deserved its own thread, since to-date I don't see one for this organic sulfur compound. I first heard about it through Dr Rhonda Patrick's various podcasts and interviews, on her website and elsewhere. She has several videos about this compound, and how a lot of the beneficial effects of cruciferous vegetables (such as reduced all-cause mortality, including cancers) come from sulforaphane and other constituent organosulfurs. A comprehensive list of the benefits of sulforaphane can be found here:39 Sulforaphane Benefits, Foods, Supplements + Broccoli Sprouts - Selfhacked

Much of the information given below is derived from animal- and laboratory-based studies. Human studies are falling behind, but will hopefully soon follow.

Apart from being effective in its own right, sulforaphane also enhances the efficacy of anti-cancer drugs including cisplatin, gemcitabine, doxorubicin, and 5-fluorouracil, toward pancreatic and prostate cancer cells, while limiting their toxicity to normal cells [R].

However, although sulforaphane was found to be safe and effective in several studies, it was not effective in 2 clinical trials [R, R].

In one study, 23 out of 28 tested bacterial and fungal species were inhibited by sulforaphane [R].
Mycobacterium abscessus is frequently found in patients with cystic fibrosis and in immunosuppressed patients. Pretreatment of macrophages with sulforaphane significantly decreased bacterial burden [R].
Human β-defensin-2 (HBD-2) plays an important role against bacterial invasion. Sulforaphane is able to increase antimicrobial peptides such as HBD-2 [R].

Inflammation has been recognized as one of the causes of depression. By reducing inflammation, sulforaphane can help combat depression.
Repeated SFN administration reversed depression- and anxiety-like behaviors in chronically stressed mice, likely by inhibiting the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory responses to stress [R, R].
In another study, Nrf2 deficiency in mice resulted in depressive-like behavior, while the induction of Nrf2 by sulforaphane had antidepressant-like effects [R].
Also, dietary intake of glucoraphanin during the juvenile and adolescent periods in mice prevented the onset of depression-like behaviors at adulthood [R].

13) Sulforaphane Protects the Brain and Restores Cognitive Function

Sulforaphane increased neuronal BDNF in mice, a factor that supports the survival of existing neurons and encourages the formation of new neurons and synapses [R].
SFN reduced brain inflammation in various animal models of pathogen-induced neuroinflammation and neurodegenerative disease [R, R, R, R].
Sulforaphane promoted microglia differentiation from pro-inflammatory M1 to anti-inflammatory M2 state. This reduced brain inflammation and restored spatial learning and coordination in rats [R].
Sulforaphane is beneficial in various pathological conditions, as it:

Sulforaphane protected against seizures and elevated the seizure thresholds in mice [R].

18) Sulforaphane Improves Schizophrenia

Sulforaphane improved performance in a learning task in outpatients with schizophrenia [R].
Methamphetamine can induce psychosis in susceptible people. Sulforaphane weakened behavioral abnormalities in mice after administration of methamphetamine or phencyclidine, suggesting that it may help with schizophrenia [R].
Sulforaphane protected against antipsychotic-induced toxicity in dopaminergic neurons [R].
19) Sulforaphane May Be Beneficial for Substance Abuse
Sulforaphane weakened behavioral and neuropathological changes associated with methamphetamine exposure in mice. Pretreatment with sulforaphane weakened acute hyperlocomotion (increase in movement) in mice after a single administration of methamphetamine [R].
Also, the development of behavioral sensitization after repeated administrations of methamphetamine was significantly reduced by pretreatment with sulforaphane [R].

20) Sulforaphane May Improve Autism Symptoms

In a clinical trial, sulforaphane improved behavior in young men with autism [R].
Sulforaphane activates genes that protect cells against oxidative stress, inflammation, and DNA-damage, all of which are associated with autism spectrum disorder [R].

21) Sulforaphane Can Protect Against GI Injury and Inflammation

SFN protects the gut against NSAID-related damage. SFN improved aspirin/NSAID-induced injury of the gut in mice, and inhibited gastric ulcers in rats [R, R, R].
Nrf2-deficient mice exhibit worse colitis symptoms, indicating that SFN can help in this condition by activating Nrf2 [R].
Indeed, in another study, treatment with SFN decreased inflammation in mice with colitis [R].

SFN can be beneficial against T-cell driven autoimmune disorders, such as multiple sclerosis-like diseases in animals, but studies in humans are still lagging. Sulforaphane significantly inhibited the development and severity of MS-like disease in mice, mitigating inflammatory infiltration and demyelination in the spinal cord [R, R]. Sulforaphane caused improvement by silencing Th17/Th1 responses within the brain/neurons [R]. NRF2-deficient mice have exacerbated pathology in this model [R]. Sulforaphane activated the Nrf2/ARE pathway, which helps combat the disease [R].

In females, low levels of estrogen, such as during menopause or after an ovary removal surgery, can lead to reduced bone mass (osteoporosis). Sulforaphane promoted bone formation and increased bone volume (∼20%) in both normal mice and mice without ovaries. Sulforaphane diminished bone resorption, thereby shifting the balance to a state favoring bone acquisition [R].

29) Sulforaphane Can Be Beneficial for Arthritis.

A sulforaphane-rich diet improved osteoarthritis in mice. Sulforaphane inhibited key metalloproteinases implicated in osteoarthritis, independently of Nrf2, and blocked inflammation through NF-κB to protect against cartilage destruction [R].
Some of the SFN effects may be mediated by Nrf2, because enhanced oxidative stress and cartilage damage were observed in Nrf2-deficient mice with arthritis [R].
SFN reduced the severity of arthritis in mice by decreasing pro-inflammatory cytokines [R].
Several inflammatory autoimmune diseases, such as rheumatoid arthritis and osteoarthritis, switch the polarization of monocytes into classically activated pro-inflammatory macrophages (M1 type). Sulforaphane blocked the inflammatory responses specific to M1 macrophages (Th1) and shifted macrophage production to M2 macrophages [R]. M2 (Th2) decrease inflammation and encourage tissue repair.

30) Sulforaphane Can Prevent Muscle Damage.

Sulforaphane prevented muscle damage in rats after acute bouts of exhaustive exercise, by acting as an indirect antioxidant in the muscle [R].

SFN protected against kidney damage in animals [R, R]. Chemotherapeutics, such as cisplatin, can be toxic to kidneys. In animals, sulforaphane prevented inflammation and kidney damage caused by cisplatin [R].

Sulforaphane increased the production of enzymes that degrade DHT [R]. SNF significantly enhanced hair regeneration in mice, and reduced testosterone and DHT levels in the blood [R]. SFN increased the amount of testosterone degrading enzymes, such as 3α-HSD, in the liver, accelerated the degradation of blood DHT, and reversed the suppression of hair growth by DHT [R].

39) Sulforaphane May Benefit Children with HGPS. Hutchinson-Gilford progeria syndrome (HGPS) is a rare childhood premature aging disorder linked to mutations in the LMNA gene. Protein clearance and autophagy are impaired in HGPS cells. SFN stimulated protein clearance by autophagy and reversed cellular phenotypic changes, both of which are the hallmarks of HGPS [R].

Sulforaphane increases the activation of many beneficial genes, including tumor suppressor genes. However, sulforaphane also activates long terminal repeats (LTRs), DNA sequences found within our genome that impair genome stability and cause mutations [R].
Consumption of broccoli sprouts by human volunteers caused a 10-fold increase in LTR activation in white blood cells. These effects are transient, and it remains to be determined whether they are biologically meaningful [R].
Other studies on human volunteers recorded no abnormal events related to broccoli sprout consumption [R].
Genotoxic effects were observed in unpublished studies with pigs fed with 600 g of raw broccoli for 12 days. These pigs had an increase in DNA strand breaks by 21% in the colon [R].
Also, after feeding raw or steamed broccoli to mice and rats, an increase in DNA adducts (cancer-causing chemicals binding to DNA) was observed [R].
However, all these effects in animals were observed for mature broccoli plant consumption. An additional benefit of broccoli sprouts is that they contain negligible quantities of indole glucosinolates, which predominate in the mature vegetable, and may give rise to degradation products (e.g., indole-3-carbinol). This can enhance tumorigenesis [R].

2) Excessive Consumption May or May Not Cause Liver Toxicity
There is a single case report of liver toxicity after drinking large amounts of broccoli juice for 4 weeks (800 ml/day). Transaminases, aspartate aminotransferase, and c-glutamyltrans-peptidase were elevated, but decreased to normal within 15 days [R].
This was also caused by consuming the mature plant and may be caused by other substances found in the broccoli plant, unrelated to sulforaphane.

Broccoli Sprouts Are the Richest Source of Sulforaphane. The amount of sulforaphane (glucoraphanin) can vary widely in vegetables [R]. Broccoli is not the only cruciferous vegetable which has SFN, but it yields the highest amounts, with glucoraphanin content around 75% of total glucosinolates [R]. Furthermore, 3-day-old broccoli sprouts contain 10 to 100 times higher levels of glucoraphanin than does a mature broccoli [R, R].

Myrosinase Is Necessary for Sulforaphane Production. The majority of SFN is formed when glucoraphanin gets processed by myrosinase, upon plant tissue damage (e.g. chopping, chewing). When plant myrosinase is inactive or absent, a small amount of SFN may still be formed by gut bacteria-derived myrosinase activity [R].

Gut bacteria, such as Bifidobacterium, Lactobacillus, and Bacteroides, have been reported to possess myrosinase-like activity [R].

Many available broccoli sprout supplements are myrosinase-inactive [R, R]. SFN absorption was sevenfold lower for glucoraphanin supplements than equivalent glucoraphanin-containing fresh broccoli sprouts with the active enzyme [R]. SFN absorption from a glucoraphanin powder devoid of myrosinase activity improved when consumed along with an active source of myrosinase (such as air-dried broccoli sprouts) [R].

Processing Inactivates Myrosinase. The bioavailability of sulforaphane from fresh broccoli is much higher than that from cooked broccoli [R]. Higher amounts of sulforaphane were found in the blood and urine when broccoli was eaten raw (bioavailability of 37%) versus cooked (3.4%) [R]. Cooking and/or blanching (during freezing process) of cruciferous vegetables inactivates myrosinase and decreases sulforaphane bioavailability [R]. Boiling for more than 1 minute, or steaming for more than 4 to 5 minutes, inactivates myrosinase [R].

Myrosinase Enhancers. Mustard seeds contain a more resilient form of myrosinase. The addition of powdered mustard seeds to heat-processed broccoli significantly increased the production of sulforaphane [R].

Avoiding Nitrile Formation. Broccoli also contains significant amounts of epithiospecifier protein (ESP), an inhibitor of myrosinase. ESP produces inactive sulforaphane nitrile. Under certain conditions, as much as 75% nitrile is created [R]. ESP is more heat sensitive than myrosinase. Steaming for 1 to 3 minutes provides less nitrile and more sulforaphane yield from a broccoli meal [R].

Sulforaphane Metabolism. Sulforaphane is rapidly absorbed, peaking in the blood as early as 1 to 3 hours after ingestion [R, R]. Once SFN is distributed, there is evidence that it can accumulate in tissues and produce anticancer blocking and suppressing effects [R]. In the blood, sulforaphane-glutathione accounts for more than 50% of total sulforaphane metabolites [R]. SFN and its metabolites are cleared from the body within 12 to 72 hours of dosing, by urinary excretion [R, R, R]. Maintenance of SFN concentrations in the body can be achieved by consuming recommended servings of cruciferous vegetables once a day [R].

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Huh! Interesting, thanks for sharing whitecoast. It seems I haven't been getting any of the benefits of eating broccoli because I steam it for way too long. I came across this article by Bulletproof on sulphoraphane as well as how to increase your intake of it and grow broccoli sprouts.

Have you ever taken the lid off a pot of broccoli or cauliflower and been hit with an unpleasant smell – something sort of like rotten eggs?

That’s the good stuff. The pungent odor you get from brassica vegetables – broccoli, cauliflower, cabbage, and Brussels sprouts – is thanks to a rockstar molecule called sulforaphane (the sulfur is what gives it its smell).

Antioxidants come up a lot at Bulletproof, and sulforaphane is one of the most potent antioxidants available. It’s an exceptionally powerful anti-inflammatory, detoxifier, and even brain enhancer. It builds stronger mitochondria, too, which means a stronger brain and body as you age.

The best part? You don’t have to take a supplement to get this precious little compound. You can find loads of sulforaphane in veggies you’re probably already eating; the key is to prepare them right. Here’s what sulforaphane does for you, and how you can upgrade your broccoli, cauliflower, and cabbage to get much more of it.

Sulforaphane + Nrf2 = supercharged antioxidant production

Every cell in your body contains a powerful protein called Nrf2. The little guy is usually sleeping, but when stress, inflammation, or another signal hits your body, Nrf2 wakes up and gets to work. It binds to something called the antioxidant response element (ARE), the master switch that controls antioxidant production. When ARE turns on, your cells start pumping out antioxidants and detox compounds like glutathione, quieting inflammation and protecting you against stress and damage.

The key to starting this whole process is waking up Nrf2. That’s where sulforaphane comes in. It’s a potent Nrf2 activator [1,2], freeing the Nrf2 protein to turn on your antioxidant production. This pathway affects your whole body, which could explain why sulforaphane does so many different things for you:

Reduces symptoms of autism. A double-blind, placebo-controlled study of men with autism found that supplementing with sulforaphane dramatically reduced symptoms, including lethargy, irritability, stereotypy, and hyperactivity [8]. Patients took the equivalent of a couple of servings of broccoli a day.

Weight loss. Activating Nrf2 increases fat burning [9], and it prevented obesity in mice fed a high-fat diet (mice did not evolve with much fat in their diets, and are notoriously bad at processing it) [10].

Kills cancer cells. Sulforaphane destroys cancer cells while simultaneously strengthening healthy mitochondria [11]. It also detoxes carcinogens [12] and kills cancer cells in Petri dishes [13], and prevents tumor growth in rats [14,15]. Recent studies have found that sulforaphane helps reverse cancer in humans, too [16], and the results are so promising that drug companies are currently testing Sulforadex, a synthetic analog of sulforaphane, as a cancer treatment.

Fortunately, you don’t need to take a drug or a supplement to get this stuff.

Top 3 ways to get sulforaphane into your diet

1. Grow your own broccoli sprouts
Sulforaphane is most potent when broccoli is sprouting before it matures into the plant you see in the produce section. The best part? You can easily and cheaply grow these at home.

Ingredients/supplies:

3 tbsp. organic broccoli sprout seeds

1 large (32-oz.) mason jar

Sprouting top

Small bowl for draining

Filtered water

Directions:

Add seeds to your clean mason jar.

Cover with about 3 inches of filtered water.

Leave the seeds to soak in water for about 12 hours (in a cool, dry place, not in the fridge or in direct sunlight).

After about 12 hours, drain the water and rinse and drain your seeds into the draining dish.

Rinse and drain your sprouts twice per day (once in the morning, once at night) until your seeds sprout (usually 5-6 days).

When your jar is full of fresh sprouts, they’re done.

Rinse and pat dry with paper towels. Store in the fridge.

Enjoy in salads, soups, and smoothies!

Recommended dose: Eat ½-1 cup of sprouts daily on salads or in soups or stews, along with some raw radish.

Time of day: Anytime

2. Steam your brassicas

The best sources of sulforaphane are broccoli sprouts or an activated sulforaphane supplement, but there’s also plenty of it in the other members of the brassica family: broccoli, cauliflower, cabbage, and Brussels sprouts. To access sulforaphane, you have to coax your veggies to release myrosinase, an enzyme that mixes with a compound called glucoraphanin to create sulforaphane.

You’ll get a little bit of sulforaphane from raw or fully cooked veg, but the sweet spot is in the middle. Light steaming (3-4 minutes) will triple the sulforaphane you absorb [17,18].

Bonus points if you slice your veggies, let them sit for a few minutes to release myrosinase, and then gently steam them.

One last thing: buy your brassica veggies fresh, not frozen. Frozen broccoli is blanched before it’s frozen. The combo deactivates myrosinase, which means no sulforaphane [19].

3. Take an activated sulforaphane supplement
Most of the sulforaphane you’ll find online requires activation by gut bacteria that aren’t common, so you probably won’t see much benefit from it. You can either buy an enzyme-activated sulforaphane or make sure to eat a bite of raw radish or cruciferous vegetable (like a broccoli stalk) to get the right living enzymes in your gut to activate the supplement.